tbuckley/cabot-search huggingface dataset:
Abstract 123: Bystander Cpr Usage In Out-of-hospital Cardiac Arrest During The Covid-19 Pandemic: Results From The Northeast Georgia Cardiac Arrest Registry
Authors: Riaz Mahmood, Abdullah Asreb, Joon Ahn
Journal: Circulation (2022)

Background: During the COVID-19 pandemic, a higher incidence of out-of-hospital cardiac arrest (OHCA) has been reported but rates of bystander CPR usage have not been studied. Due to the COVID-19 pandemic, bystanders may be reluctant to perform CPR due to risk of infection and due to social isolation measures, there may be less bystanders present to perform CPR.Objective: The purpose of the study was to study rates of bystander CPR usage in out-of hospital cardiac arrest (OHCA) during the COVID-19 pandemic and to evaluate for any association between bystander CPR usage and increasing COVID-19 infection during 2020 and 2021. Methods: We performed a retrospective study of the Northeast Georgia Cardiac Arrest Registry to compare bystander CPR usage for all patients presenting to Northeast Georgia Medical Center in Gainesville, Georgia with OHCA from 14 surrounding counties of northeast Georgia from March 2019 to December 2021. Results: A total of 18,421 and 18,678 COVID-19 infections were reported in Hall County between Mar-Dec 2020 and Jan-Dec 2021, respectively. A total of 228 cardiac arrests occurred in 2019, 273 in 2020, and 268 in 2021. Overall bystander CPR usage was 44% in 2019, 43% in 2020, and 47% in 2021, p = .64. Before COVID-19 the bystander CPR usage was 43% and 46% during, p = 0.44. There was no significant correlation between bystander CPR usage and COVID-19 infections in Hall County (r = 0.06, p = 0.79). Multivariable logistic regression model demonstrated that initial shockable rhythm (p &lt; 0. 001) was the strongest predicator of bystander CPR (table 1). Conclusions: Bystander CPR usage in OHCA in the northeast Georgia region remained constant despite the COVID-19 pandemic. There were no significant differences in bystander CPR usage in OHCA prior to or during COVID-19 pandemic. Additional studies are needed to evaluate for possible variables which may be contributing to initial shockable rhythm as the strongest predicator of bystander CPR.
Abstract 11790: Behavioral Interviewing for Graduate Medical Education Programs in the Covid/Virtual Interviewing Era
Authors: Dipanjan Banerjee, Zia Khan, Todd B Seto, David Singh, Ted Leon, Peter Tsai, Anne Kemble
Journal: Circulation (2022)

Introduction: Coronavirus pandemic restrictions have affected social interactions, and the process of interviewing candidates for positions in graduate medical education (GME) programs is no exception. The threat of such restrictions is that candidates and programs may have less ability to achieve the best mutual fit. However, the pandemic also allows opportunities to rethink how we approach the interview process, and potentially optimize it. Behavioral interviewing (BI) techniques are one approach to both constructively address pandemic restrictions, and potentially improve recruitment to GME programs. Hypothesis: We hypothesized that behavioral interviewing could be integrated into a virtual interviewing process. Methods: We reviewed the behavioral interviewing process, and described how we integrated it into our virtual program recruitment of 91 candidates in 2020 and 2021. We elicited interviewer and interviewee feedback regarding the behavioral interviewing process, and analyzed discrepancies between ranks by traditional and behavioral interviewers. Results: Behavioral interviewing was viewed as highly positive or positive by 100% of interviewers and 93% of interviewees in 2021. The average discrepancy between standard and behavioral interview rank placement was 2.67 (SD 2); with 11 (8%) candidates exhibiting a significant rank divergence (&gt; 5 rank orders). The best agreement between behavioral and traditional interviewer rank orders was in the top tertile of candidates. Conclusions: Behavioral interviewing can successfully be implemented in a virtual GME recruitment format, and provides opportunities to optimize program and candidate cohesion.
Abstract 11581: False Positive Troponin Elevation Due to Heterophile Antibody
Authors: Morgan Chien-Hale, Hannah Bernstein
Journal: Circulation (2022)

Introduction: While highly specific, false positive Troponin I (TnI) can be caused by heterophile antibodies, autoimmune phenomena, and fibrin interference. The overreliance on TnI levels can lead to unnecessary patient work-up. Here we present a case of chronically elevated troponin over several hospitalizations most consistent with viral heterophile antibody cross reactivity. Case: A 71-year-old man with diabetes and polio-related paraplegia was admitted for pharyngitis. Initial TnI assay was significantly elevated at &gt;90 (normal &lt; 0.04 ng/mL) with a CK-MB of 21.7 (normal &lt;20.0 U/L). ECG showed no evidence of ischemia (Figure 1). He had similar TnI elevation on two prior hospitalizations, with no significant coronary artery disease on angiography. Despite the absence of chest pain and normal ECG and TTE, myocardial perfusion stress test was performed due to the elevation in CK-MB, which was negative for ischemia (Figure 2). Troponin T, a sendout lab, was &lt;12 ng/L. Patient was later confirmed to have positive CMV IgG and positive EBV viral capsid and nuclear antigen IgG, supporting the mechanism of heterophile antibody cross reactivity as the mechanism for false positive troponin. Discussion: Our case demonstrates a growing literature of patients presenting with chronically elevated TnI unrelated to myocyte damage. Focus of troponin levels without consideration of overall clinical picture and previous medical history can lead to unnecessarily invasive and expensive testing. For this patient, elevated troponin led to unnecessary testing and prolonged hospital admissions despite consistently negative cardiac workup. Heterophile cross reactivity can lead to false positive TnI in 1:2000 patients. If elevated troponin is concerning for a false positive, evaluation through other markers should be considered before undergoing more invasive procedures.
Abstract 12188: Acute Bi-Ventricular Dysfunction and Cardiogenic Shock Following Transcatheter Mitral Valve Repair
Authors: Abdul H Azizi, Fazal Ali, Erik Marshall, Wasif Qureshi
Journal: Circulation (2022)

Background: For patients with functional mitral regurgitation (MR) who remain symptomatic despite GDMT, transcatheter mitral valve repair (TMVR) is emerging as a less-invasive alternatives and can improve symptoms and longevity. We describe a rare case of cardiogenic shock following TMVR. Case: 63-year-old male with PMHx of CAD with prior CABG, severe MR with EF of 40% developed progressive dyspnea and evaluated for TMVR with a Mitraclip device. TEE pre-deployment confirmed moderate to severe MR (Figure 1). Right heart catheterization revealed preserved cardiac index. Intraoperative TEE after deployment showed improved MR. Post-procedure, he developed respiratory distress and progressive hypotension requiring vasopressors and inotropes. TTE showed mild MR with severely reduced biventricular function (EF 10%). Cardiac catheterization showed a severely reduced CO/CI 3.1/1.42. Mechanical circulatory support was initiated with Impella CP due to persistent cardiogenic shock. By POD 3, he was off all inotropes and MCS was discontinued. His EF recovered to 45% during a 3- month visit. Decision Making: Causes of cardiogenic shock post mitral valve procedure include cardiac tamponade, acute mitral stenosis, intrathoracic hemorrhage and afterload mismatch. Afterload mismatch is due to reduction in left ventricular stroke volume when preload is not compensated for an acute increase in afterload. It is a known complication after mitral valve surgery; however it is rarely seen post TMVR. This patient likely experienced afterload mismatch after his mitral clipping procedure as evidenced by the acute, transient decline in LVEF (55% to 10%). Conclusion: Afterload mismatch is a rare phenomenon that can cause cardiogenic shock post percutaneous mitral repair procedures. It must be rapidly addressed with inotropic and/or mechanical support to prevent permanent end organ dysfunction and circulatory collapse. Prompt treatment allows for excellent recovery.
Abstract 11593: The Critical Role of Transthoracic Echocardiography in the Evaluation of Cardiogenic Shock and Takotsubo Cardiomyopathy
Authors: Jenna Spears, Yousif Al-Saiegh, farah olleik, Roy Taoutel, John Steers
Journal: Circulation (2022)

Introduction: Cardiogenic shock occurs in 10% of patients with takotsubo cardiomyopathy (TTC) as a result of severe systolic dysfunction, or left ventricular outflow tract (LVOT) obstruction. Methods: Case report and review of the literature. Results: A 62-year-old female with a history of hypertension and diabetes mellitus presented with lightheadedness, shortness of breath, and chest discomfort. She was hemodynamically unstable, tachycardic, and hypotensive (70/40 mmHg). Her EKG showed sinus tachycardia at 101 BPM with 1 mm ST depression in leads II, III, AVF; V3-V6. Chest radiograph revealed pulmonary edema. High-sensitive troponin was 146.7. She was intubated for respiratory distress and had rapidly increasing vasopressor requirements. Emergent coronary angiography revealed nonobstructive coronary artery disease. A left ventriculogram revealed apical ballooning with an estimated ejection fraction of 25%, consistent with TTC. Transthoracic echocardiogram (TTE) showed severe mid and apical LV hypokinesis with basal hyperkinesis. Additionally, systolic anterior motion (SAM) of the mitral valve (MV) was noted, with a peak LVOT gradient of 7 mmHg. The patient improved clinically, and all support was weaned off. However, she later acutely developed recurrent respiratory distress and hypotension. Repeat TTE showed LVOT obstruction with a gradient of 40 mmHg due to increased basal hyperkinesis and SAM. The choice of vasopressor was switched from norepinephrine to phenylephrine to reduce the obstruction. She clinically improved and metoprolol succinate was added to reduce basal hypercontractility and improve left ventricular filling. Conclusions: Differentiating the mechanism of shock in TTC can easily be accomplished with TTE, and is essential to guiding treatment. The initial acute systolic dysfunction was effectively managed with norepinephrine, dopamine, and an intra-aortic balloon pump. She later developed LVOT obstruction as her systolic function improved. This was recognized with TTE and led to an appropriate change in vasopressor, as norepinephrine would have worsened the obstruction. This highlights the importance of early TTE in patients presenting with undifferentiated shock, especially when TTC is suspected.
Abstract 11681: Engineering of an IPSC Derived Perfusable and Thick Three-Layer Cardiac Tissue
Authors: Kenji Miki, Joshua R Gershlak, Harald Ott
Journal: Circulation (2022)

Introduction: The left ventricular wall is an approximately 1 cm thick tissue composing of vascular networks and three distinct layers: the endocardium, the myocardium, and the epicardium. Engineering of a perfusable and thick three-layer cardiac tissue from human induced pluripotent stem cells (hiPSCs) has not been accomplished to date. Here, we describe formation of a perfusable and thick three-layer engineered cardiac tissue (PTTL-ECT) using additive and subtractive manufacturing. Methods: hiPSCs were differentiated into endocardial (Endo) cells, cardiomyocytes (CMs) and epicardial (Epi) cells. To create a perfusable vascular network in an engineered cardiac tissue, we used a water-soluble heat extruded material to print a sacrificial pattern that would eventually dissolve and become a vascular lumen. By casting hydrogels and the three types of cells derived from hiPSCs, we stacked the endocardial layer, myocardial layer, and epicardial layer mimicking the architecture of the ventricular wall . We then compared PTTL-ECT with engineered tissues without perfusable vascular channels (TTL-ECT) and single layer perfused tissues (PTSL-ECT). Results: Purity of hiPSC derived-Endo cells, -CMs, and -Epi cells reached 96.98±1.33% for NFATC1 + and CD31 + Endo-cells, 83.95±1.77% for cTNT + CMs, and 97.75±1.75% for WT1 + Epi-cells, respectively. The PTTL-ECT had 1.2 cm thickness at day 1 after casting. Histological analysis of the TTL-ECT without vascular channel showed a necrotic core with only the outermost cell layer survived after 4 weeks of culture. Addition of the vascular channel enabled cell survival across the thickness of the entire PTTL-ECT, while the three-layered structure remained intact over four weeks of perfusion culture. CMs in the PTTL-ECT showed enhanced maturity in terms of gene expression profiles, sarcomere lengths and contraction force compared with PTSL-ECT. Conclusions: By combining additive and subtractive manufacturing methods, we successfully generated a perfused, three layers thick cardiac graft that maintained architecture and viability over extended culture periods. The PTTL-ECT could be an useful in vitro model that mimic the native ventricular tissue in disease modeling and drug testing.
Abstract 12535: Associations Between Apolipoprotein (b) and Lipoprotein (a) With Coronary Calcium Scoring
Authors: Adel Hajj Ali, Wynne Zheng, Michael Nakhla, Leslie Cho, Raul Seballos, Richard S Lang, Steven Feinleib, Scott D Flamm, Paul SCHOENHAGEN, Tom Kai Ming K Wang, Steven E Nissen, Milind Y Desai
Journal: Circulation (2022)

Introduction: Apolipoprotein B (ApoB) and Lipoprotein a (Lpa) are emerging as important markers of coronary artery disease (CAD). In subjects without documented CAD, we assessed the association between ApoB and Lpa with coronary artery calcium scoring (CACS). Methods: We included 5324 subjects (age 57±8 years ,76% male &amp; 87% white) referred for CACS in a primary prevention clinic between 3/2016 and 10/2021. 10-year multiethnic study on subclinical atherosclerosis CACS (MESA-CACS) risk score was calculated as 0, 1-4.99, 5-9.99 and &gt;10%. ApoB (mg/dl) was divided into &lt;104, 104-127 and &gt;127, while Lpa (mg/dl) was divided into≤40 and &gt;40. Additionally, Lpa was divided based on 60, 70 and 90 mg/dl cutoffs. Results: ApoB was significantly associated with MESA-CAC risk score (p&lt;0.001); while Lpa had a borderline association (Table) (p=0.09). A significantly higher proportion of subjects with normal ApoB were in 0 MESA-CACS risk category (87%), with no difference in other risk categories (Figure 1A). Almost 25% patients with 0 MESA-CACS had Lpa of &gt;40, with no significant difference between normal vs. elevated Lpa across MESA-CACS categories (Figure 1B). No significant difference was noted among the MESA-CACS categories with p-values of 0.284, 0.672 and 0.392 for Lpa cutoffs of 60, 70 and 90 mg/dl respectively. Despite a CACS of 0, 793 (15%) subjects had Lpa&gt;40, while 690 (13%) had a CACS &gt;75th percentile despite Lpa≤40. Conclusions: ApoB was significantly associated with MESA-CACS score, while Lpa only showed a weak association. Hence the addition of Lpa could add synergistic value to CACS in atherogenic risk. stratification Fig1 Distribution of ApoB (A) and Lpa(B) across MESA-CACS groups
Abstract 12364: Exogenous Sphingosine-1-Phosphate Restores Nitric Oxide-Mediated Flow-Induced Dilation During Acute Inhibition of Ceramide Formation
Authors: Gopika Senthilkumar, Boran Katunaric, Henry Bordas-Murphy, Julie K Freed
Journal: Circulation (2022)

Our previous work has shown that chronic exposure to ceramide, a sphingolipid that when elevated in plasma is an independent risk factor major adverse cardiac events, causes microvascular endothelial dysfunction in arterioles collected from healthy adult patients. This presents as a change in the mediator of flow-induced dilation (FID) from the vasoprotective nitric oxide (NO) to the pro-atherosclerotic hydrogen peroxide (H 2 O 2 ). Despite the known detrimental effects of ceramide, its metabolite sphingosine-1-phosphate (S1P) can promote NO formation. However, shear-induced ceramide formation is also necessary for maintaining NO-mediated FID, as arterioles from healthy individuals transition to H 2 O 2 -mediated FID during inhibition of the ceramide-forming enzyme neutral sphingomyelinase (NSmase). We hypothesize that the transition in mediator is due to the loss of acute S1P production, and thus addition of exogenous S1P can prevent microvascular endothelial dysfunction during inhibition of NSmase. Human arterioles (100-250μm) were dissected from otherwise discarded adipose tissue from healthy patients undergoing surgery. Videomicroscopy was used to assess vascular function in vitro . Microvessels were pre-constricted with endothelin-1, and changes in internal diameter were measured following exposure to increased levels of flow. Dilation to flow was significantly impaired in the presence of the NO-synthase inhibitor L-NAME (100μM, 30 min) when healthy human arterioles were treated acutely with S1P (1μM, 30 min) in the presence of the NSmase inhibitor, GW4869 (10μM, 30 min), compared to GW4859 alone (% maximal diameter±SEM, 5.1±8.7, n=4 vs 70.1±5.3, n=4; p=0.001, 2-way ANOVA). Whereas, the presence of PEG-catalase, an enzyme that breaks down H 2 O 2 , had no effect (85.0±4.3; n=3). These data highlight the importance of S1P in maintaining NO signaling during exposure to shear and strengthens the concept that the conversion of ceramide to S1P is critical in promoting a quiescent endothelium.
Abstract 12715: Role of Novel Long Non-Coding RNA BAZ1A-AS1 in Neointima Formation in Human Saphenous Vein Graft Disease
Authors: David S Kim, Stephen Cave, Jacob Greenway, Rohan Mundkur, Brandee Goo, Samah Ahmadieh, Ragheb Harb, Hong Shi, Yang Shi, Vijay Patel, Richard Lee, Xiaochun Long, Joseph M Miano, Ha W Kim, Neal L Weintraub
Journal: Circulation (2022)

Introduction: Saphenous veins (SVs) are frequently used in CABG surgery, but over 50% of the SV grafts fail in the first 10 years after surgery due to neointima formation. Long non-coding RNAs (lncRNAs) have emerged as attractive therapeutic targets and biomarkers for cardiovascular disease. However, studies on their role and mechanisms in humans are limited. This study aimed to unravel epigenetic mechanisms of neointima formation in human SVs and investigate the role of candidate lncRNAs in key vascular cell functions pertinent to neointima formation. Methods and Results: By using an ex vivo model of human SV graft disease wherein segments of human SV are incubated in tissue culture, we performed RNA-sequencing on human SV with and without neointima formation to interrogate the global transcriptomic changes, and determined 699 differentially expressed novel lncRNAs during neointimal formation. We then identified BAZ1A-antisense (AS)1 as a novel lncRNA highly upregulated during neointima formation. BAZ1A-AS1 overlaps antisense to its cis- regulatory gene, BAZ1A , which was reported to play a role in oxidative stress and DNA damage repair response. We found that one isoform of BAZ1A-AS1 primarily localizes to the nucleus of VSMCs. Interestingly, UV exposure of vascular smooth muscle cells (VSMCs) isolated from human SV induced significant upregulation of BAZ1A and BAZ1A-AS1, suggesting that BAZ1A-AS1 could be associated with chromatin repair processes activated during neointima formation. To investigate whether BAZ1A-AS1 can regulate VSMC functions pertinent to neointima formation, VSMCs were transfected with BAZ1A-AS1 antisense gapmers. Knockdown of BAZ1A-AS1 showed reduced cell proliferation and migration, and increased cell death and DNA damage in VSMCs. Furthermore, role of BAZ1A during neointima formation in vivo is currently under investigation in a carotid artery ligation model using BAZ1A knockout mice. Conclusions: We identified BAZ1A-AS1 as a novel lncRNA associated with neointima formation in human SV, and targeted inhibition of BAZ1A-AS1 or its cis-regulator gene BAZ1A could be a promising strategy for SV graft disease.
Abstract 11411: Anti-MiR-510-3p Alleviates Endothelial Dysfunction in Preeclampsia Induced Rat Model B\by Regulating PTEN and Its Signalling Pathways
Authors: Sushmaa Chandralekha Selvakumar, Auxzilia Preethi K, Durairaj Sekar
Journal: Circulation (2022)

Introduction: Preeclampsia (PE) is a pregnancy complication associated with multi-organ endothelial dysfunction. The hypoxia resulting from vascular remodelling lowers blood flow in placenta leading to high mortality and morbidity in PE. Studies on molecular and signalling pathways involved in PE could pave way for early diagnosis and treatment. miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in PE patients compared to normal. Hypothesis: We hypothesize that miR-510-3p targets PTEN in regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential biomarker and therapeutic target. We elucidate the therapeutic role of antimiR-510-3p in PE and its interaction with miR-510-3p and associated signalling pathways in PE induced rat model. Methodology: The proliferation, migration, invasion and apoptosis of HTR/SVNeo cells were analyzed for miR-510-3p, PTEN and antimiR-510-3p. Luciferase assay confirmed PTEN as target for miR-510-3p. The expression of miR-510-3p and PTEN/PI3K/AKT/eNOS/mTOR axis was analysed using qPCR and western blot. Deoxycorticosterone (DOCA) (12.5 mg/kg before mating and 6.5 mg/kg after mating twice a week) and 0.9% salt ad libitum were used to develop a PE induced rat model (SD rats). By quantifying miR-510-3p levels in PE group, the doses of antimiR-510-3p for the dose-dependent study were determined. The final effective dose was fixed from the dose-response curve. To examine the hypoxia and hypertrophy, histological analysis was performed in paraformaldehyde fixed tissues. Results: Significant changes were observed in the BP, proteinuria and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets PTEN leading to endothelial dysfunction, hypoxia and hypertrophy in PE, while treatment with antimiR-510-3p exhibits a significant reduction in PE in PE induced rat model. The gene and protein expression analysis revealed a significant correlation between miR-510-3p, PTEN and antimiR-510-3p in PE. Conclusion: Thus our findings from in vitro and in vivo suggest miR-510-3p as a potential biomarker and therapeutic target and antimiR-510-3p as a novel therapeutic molecule for PE.